Characterization of CART neurons in the rat and human hypothalamus

Cocaine- and amphetamine-regulated transcript (CART) is a recently describe d neuropeptide widely expressed in the rat brain. CART mRNA and peptides ar e found in hypothalamic sites such as the paraventricular nucleus (PVH), th e supraoptic nucleus (SON), the lateral hypothalamic area (LHA), the dorsom edial nucleus of the hypothalamus (DMH), the arcuate nucleus (Arc), the per iventricular nucleus (Pe), and the ventral premammillary nucleus (PMV). Int racerebroventricular administration of recombinant CART peptide decreases f ood intake and CART mRNA levels in the Are are regulated by leptin. Leptin administration induces Fos expression in hypothalamic CART neurons in the P VH, the DMH, the Arc, and the PMV. In the current study, we used double lab el in situ hybridization histochemistry to investigate the potential direct action of leptin on hypothalamic CART neurons and to define the chemical i dentity of the hypothalamic CART neurons in the rat brain. We found that CA RT neurons in the Arc, DMH, and PMV express long form leptin-receptor mRNA, and the suppressor of cytokine signaling-3 (SOCS-3) mRNA after an acute do se of intravenous leptin. We also found that CART neurons in the parvicellu lar PVH, in the DMH and in the posterior Pe coexpress thyrotropin-releasing hormone (TRH) mRNA. CART neurons in the magnocellular PVH and in the SON c oexpress dynorphin (DYN), and CART cell bodies in the LHA and in the poster ior Pe coexpress melanin-concentrating hormone (MCH) and glutamic acid deca rboxylase (GAD-67) mRNA. In the Are, a few CART neurons coexpress neurotens in (NT) mRNA. In addition, we examined the distribution of CART immunoreact ivity in the human hypothalamus. We found CART cell bodies in the PVH, in t he SON, in the LHA, in the Are (infundibular nucleus) and in the DMH. We al so observed CART fibers throughout the hypothalamus, in the bed nucleus of the stria terminalis, and in the amygdala. Our results indicate that leptin directly acts on CART neurons in distinct nuclei of the rat hypothalamus. Furthermore, hypothalamic CART neurons coexpress neuropeptides involved in energy homeostasis, including MCH, TRH, DYN, and NT. The distribution of CA RT cell bodies and fibers in the human hypothalamus indicates that CART may also play a role in the regulation of energy homeostasis in humans. (C) 20 01 Wiley-Liss, Inc.